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- Foltynie, T, et al.
(författare)
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MRI-guided STN DBS in Parkinson's disease without microelectrode recording : efficacy and safety
- 2011
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Ingår i: Journal of Neurology, Neurosurgery and Psychiatry. - : BMJ. - 0022-3050 .- 1468-330X. ; 82:4, s. 358-363
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Tidskriftsartikel (refereegranskat)abstract
- Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is a commonly employed therapeutic procedure for patients with Parkinson's disease uncontrolled by medical therapies. This series describes the outcomes of 79 consecutive patients that underwent bilateral STN DBS at the National Hospital for Neurology and Neurosurgery between November 2002 and November 2008 using an MRI-guided surgical technique without microelectrode recording. Patients underwent immediate postoperative stereotactic MR imaging. The mean (SD) error in electrode placement was 1.3 (0.6) mm. There were no haemorrhagic complications. At a median follow-up period of 12 months, there was a mean improvement in the off-medication motor part of the Unified Parkinson's Disease Rating Scale (UPDRS III) of 27.7 points (SD 13.8) equivalent to a mean improvement of 52% (p<0.0001). In addition, there were significant improvements in dyskinesia duration, disability and pain, with a mean reduction in on-medication dyskinesia severity (sum of dyskinesia duration, disability and pain from UPDRS IV) from 3.15 (SD 2.33) pre-operatively, to 1.56 (SD 1.92) post-operatively (p=0.0001). Quality of life improved by a mean of 5.5 points (median 7.9 points, SD 17.3) on the Parkinson's disease Questionnaire 39 summary index. This series confirms that image-guided STN DBS without microelectrode recording can lead to substantial improvements in motor disability of well-selected PD patients with accompanying improvements in quality of life and most importantly, with very low morbidity.
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| 2. |
- Scott, Robert A., et al.
(författare)
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A genomic approach to therapeutic target validation identifies a glucose-lowering GLP1R variant protective for coronary heart disease
- 2016
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Ingår i: Science Translational Medicine. - : American Association for the Advancement of Science (AAAS). - 1946-6234 .- 1946-6242. ; 8:341
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Tidskriftsartikel (refereegranskat)abstract
- Regulatory authorities have indicated that new drugs to treat type 2 diabetes (T2D) should not be associated with an unacceptable increase in cardiovascular risk. Human genetics may be able to guide development of antidiabetic therapies by predicting cardiovascular and other health endpoints. We therefore investigated the association of variants in six genes that encode drug targets for obesity or T2D with a range of metabolic traits in up to 11,806 individuals by targeted exome sequencing and follow-up in 39,979 individuals by targeted genotyping, with additional in silico follow-up in consortia. We used these data to first compare associations of variants in genes encoding drug targets with the effects of pharmacological manipulation of those targets in clinical trials. We then tested the association of those variants with disease outcomes, including coronary heart disease, to predict cardiovascular safety of these agents. A low-frequency missense variant (Ala316Thr; rs10305492) in the gene encoding glucagon-like peptide-1 receptor (GLP1R), the target of GLP1R agonists, was associated with lower fasting glucose and T2D risk, consistent with GLP1R agonist therapies. The minor allele was also associated with protection against heart disease, thus providing evidence that GLP1R agonists are not likely to be associated with an unacceptable increase in cardiovascular risk. Our results provide an encouraging signal that these agents may be associated with benefit, a question currently being addressed in randomized controlled trials. Genetic variants associated with metabolic traits and multiple disease outcomes can be used to validate therapeutic targets at an early stage in the drug development process.
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| 3. |
- Hariz, Gun-Marie, et al.
(författare)
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Gender differences in quality of life following subthalamic stimulation for Parkinson's disease
- 2013
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Ingår i: Acta Neurologica Scandinavica. - : Wiley-Blackwell. - 0001-6314 .- 1600-0404. ; 128:4, s. 281-285
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Tidskriftsartikel (refereegranskat)abstract
- Objectives - Surveys of subthalamic nucleus (STN) deep brain stimulation (DBS) for Parkinson's disease (PD) have shown that this procedure is roughly twice more common in men than in women. Here, we investigate possible differences between women and men undergoing STN DBS, with respect to health-related quality of life.Materials and methods - Forty-nine consecutive patients (18 women) received STN DBS. The impact of PD and its surgical treatment was compared between women and men, before and at mean of 19 +/- 11months after surgery, using the Unified Parkinson Disease Rating Scale (UPDRS) and the Parkinson's Disease Questionnaire-39 (PDQ-39).Results - Duration of disease at surgery and off-medication scores of the motor part of the UPDRS were similar in women and men. At baseline, women had lower doses of dopaminergic medication than men, experienced more disability due to dyskinesias, had more sensory symptoms and perceived more difficulties in mobility. Following DBS, both men and women showed equal and significant (P<0.001) improvement in off-medication scores on the UPDRS III. On the PDQ-39, women expressed improvement in ADL to a greater extent than men. Moreover, women but not men showed a positive effect on mobility, stigma and cognition as well as on the summary score of PDQ-39.Conclusions - Although STN DBS results in equal degree of motor improvement between women and men, health-related quality of life seems to improve to a greater extent in women.
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| 4. |
- Nakajima, Takeshi, et al.
(författare)
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MRI-Guided subthalamic nucleus deep brain stimulation without microelectrode recording : can we dispense with surgery under local anaesthesia?
- 2011
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Ingår i: Stereotactic and Functional Neurosurgery. - Basel : Karger. - 1011-6125 .- 1423-0372. ; 89:5, s. 318-325
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Tidskriftsartikel (refereegranskat)abstract
- Aims: Subthalamic nucleus (STN) deep brain stimulation (DBS) for Parkinson's disease (PD) is traditionally performed under local anaesthetic (LA). STN visualization and routine validation of electrode location on stereotactic MRI may allow surgery under general anaesthesia (GA). This study compares the clinical outcome of MRI-guided STN DBS performed under LA or GA in a consecutive patient series. Methods: Unified Parkinson's Disease Rating Scale motor scores (UPDRS-III) in 14 GA patients (mean age 56.1 years, disease duration 13.8 years) were compared with those of 68 LA patients (mean age 57.5 years, disease duration 15.2 years). Results: Baseline UPDRS-III were worse in the GA group, both on medication (GA: 20.9 +/- 10.8; LA: 13.2 +/- 7.8, p < 0.01) and off medication (GA: 57.9 +/- 16.6; LA: 48.2 +/- 15.7, p < 0.05). On stimulation off medication motor scores significantly improved in both groups (GA: 27.3 +/- 11.8, mean 12-month follow-up; LA: 23.7 +/- 11.8, mean 14-month follow-up). The percentage improvement was similar in both groups (GA: 52.8%; LA: 50.8%, p = 0.96). Transient surgical complications occurred in 1 GA and 7 LA patients. Conclusions: MRI-guided STN DBS under GA with routine stereotactic verification of lead location did not have a negative effect on efficacy or safety. Surgery under GA is a viable option in patients who would find it hard to tolerate awake surgery due to disease severity, comorbidities or anxiety. Copyright (C) 2011 S. Karger AG, Basel
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